- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02366663
BEAM vs. 90-Yttrium Ibritumomab Tiuxetan (Zevalin®)/BEAM With ASCT for Relapsed DLBCL (SPINOZA)
SPINOZA / שפינוזה. Study With Preparatory INduction Of Zevalin in Aggressive Lymphoma. A Randomized Phase 3 Study of BEAM Versus 90Yttrium Ibritumomab Tiuxetan (Zevalin) / BEAM in Patients Requiring ASCT for Relapsed DLBCL
Study Overview
Status
Detailed Description
PRIMARY OBJECTIVES: I. To compare overall survival (OS) between the two transplant arms, with at least a two year of follow-up. SECONDARY OBJECTIVES: I. To compare progression-free survival (PFS), complete response (CR) and partial response (PR) proportion at day 100, time to hematopoietic recovery, incidence of infection, grade III-IV toxicities, treatment-related mortality, incidence of myelodysplastic syndrome (MDS), and secondary acute myelogenous leukemia (AML).
OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive rituximab intravenously (IV) on days -21 and -14, and 90-yttrium ibritumomab tiuxetan IV on day -14. Patients also receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours twice daily (BID) on days -5 to -2; etoposide IV over 1 hour BID or once daily (QD) on days -5 to -2; and melphalan IV on day -1. Patients then undergo peripheral blood stem cell (PBSC) transplant on day 0. ARM II: Patients receive BEAM as in Arm I and undergo PBSC transplant on day 0.
After completion of study treatment, patients are followed up weekly for 30 days, 100 days, 6 months, 1 year, every 3 months for 1 year, and then annually for 3 years.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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-
California
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Duarte, California, United States, 91010
- City of Hope Medical Center
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New York
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New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients with CD20 positive diffuse large B-cell lymphoma as confirmed by a pathological biopsy report.
- Patients who are candidates for autologous stem-cell transplantation due to primary refractory or first relapse of disease.
- Patients must have chemo-sensitive disease achieving at least partial response (Cheson 2007 criteria) to last chemotherapy.
- Patients with adequate autologous stem cell collection for transplantation (target >= 2.5 x 10^6 CD34+ cells/kg).
- Patients must sign written informed consent.
- Adequate birth control in fertile patients.
- All prior chemotherapy completed at least three weeks before study treatment.
- Marrow involvement less than 25% at transplantation, no limitation on blood counts (low platelet count allowed).
- Negative HIV antibody.
Exclusion Criteria:
- Chemo-refractory disease as determined by less than partial response (Cheson 2007 Criteria) to last chemotherapy.
- Two or more relapses after initial response to induction chemotherapy.
- High-grade transformation from earlier diagnosis of low-grade lymphoma. Patients with "De Novo" Transformed DLBCL, defined as DLBCL only on lymph node biopsy and a discordant marrow with para-trabecular small cells at first diagnosis of lymphoma, are eligible if adherent to all other selection criteria.
- Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit.
- Creatinine > 2.0 mg/dl.
- KPS < 70.
- Uncontrolled infection.
- Pregnancy or lactation.
- Abnormal lung diffusion capacity (DLCO < 40% predicted).
- Severe cardiovascular disease; New York Heart Association (NYHA) Functional Classification ≥2.
- Active CNS disease involvement.
- Presence of any other malignancy or history of prior malignancy within 5 years of study entry. Within 5 years, patients treated for Stage I or II cancers are eligible provided they have a life expectancy > 5 years in relation to this prior malignance. The 5-year exclusion rule does not apply to-non melanoma skin tumors and in situ cervical cancer.
- Pleural effusion or ascites > 1 liter.
- Known hypersensitivity to rituximab.
- Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate.
- Prior radioimmunotherapy.
- Prior autologous or allogeneic HSCT.
- Active evidence of Hepatitis B or C infection; Hepatitis B surface antigen positive.
- Patients who have had prior radiation to the lung will be excluded from the study, although mediastinal irradiation will be permitted if minimal lung is in the treatment volume.
- Patients who have received >500cGy radiation to the kidneys will be excluded from the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I (ZBEAM)
Patients receive rituximab IV on days -21 and -14, and 90-yttrium ibritumomab tiuxetan IV on day -14.
Patients also receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1.
Patients then undergo autologous hematopoietic stem cell transplant on day 0.
|
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
0.4 mCi/kg given IV
Other Names:
Autologous Hematopoietic Stem Cell Transplantation (ASCT)
Other Names:
|
Active Comparator: Arm II (BEAM)
Patients receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1.
Patients then undergo autologous hematopoietic stem cell transplant on day 0.
|
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Autologous Hematopoietic Stem Cell Transplantation (ASCT)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: Measured from randomization to date of death or last follow up date, whichever occurs first, for up to 5 years post randomization
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Survival estimates will be calculated using the Kaplan-Meier method
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Measured from randomization to date of death or last follow up date, whichever occurs first, for up to 5 years post randomization
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival
Time Frame: Measured from randomization until death, relapse/progression, receipt of anti-lymphoma therapy, or last follow up whichever comes first, for up to 5 years post randomization
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Survival estimates will be calculated using the Kaplan-Meier method
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Measured from randomization until death, relapse/progression, receipt of anti-lymphoma therapy, or last follow up whichever comes first, for up to 5 years post randomization
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Time to Progression
Time Frame: Up to 5 years
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Time-to-event will be measured from the date of ASCT.
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Up to 5 years
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Number of Patients With Complete or Partial Response at Day 30
Time Frame: Day 0 to Day +30 post-HCT
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Definition of disease status is based on the article of Revised Response Criteria for Malignant Lymphoma Response Definitions for Clinical Trials (Cheson et al, 2007).
Tests used for evaluation of disease status would be physical examination, laboratory testing, bone marrow testing, bone marrow biopsy and aspirate, PET scan, and CT scans of neck, chest, abdomen and pelvis as indicated.
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Day 0 to Day +30 post-HCT
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Time to Neutrophil Engraftment
Time Frame: Day 0 to Day 100 post-HCT
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Time to neutrophil engraftment will be compared between treatment arms using a log-rank test, and the cumulative incidence curves will be estimated.
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Day 0 to Day 100 post-HCT
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Incidence of Infection
Time Frame: Day 0 to Day +100 post-HCT
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Microbiologically documented infections will be reported by site of disease, date of onset, severity, and resolution, if any.
The incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each patient.
The proportion of patients developing infections will be compared between treatment arms.
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Day 0 to Day +100 post-HCT
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Incidence of Non-relapse Mortality (NRM) Defined as Death Occurring in a Patient From Causes Other Than Relapse or Progression
Time Frame: From randomization until non-disease related death, or last follow-up, whichever comes first, assessed up to 5 years
|
The cumulative incidence of NRM will be estimated using the method described by Gooley et al.
Differences between cumulative incidence curves in the presence of a competing risk will be tested using the Gray method.
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From randomization until non-disease related death, or last follow-up, whichever comes first, assessed up to 5 years
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Cumulative Incidence of Secondary Malignancies
Time Frame: Up to 5 years
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Incidence of myelodysplastic syndrome (MDS), and secondary acute Myelogenous leukemia (AML) will be compared between the treatment arms using Gray's test.
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Up to 5 years
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Time to Platelet Engraftment
Time Frame: Day 0 to Day 100 post-HCT
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Time to platelet engraftment will be compared between treatment arms using a log-rank test, and the cumulative incidence curves will be estimated.
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Day 0 to Day 100 post-HCT
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Number of Patients With Grade 3-5 Toxicities Graded by the NCI CTCAE Version 4.0
Time Frame: Day -21 to Day +100 post-HCT
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Observed toxicities will be summarized in terms of type and severity.
In accordance with the secondary study objectives, descriptive analyses on these data will be performed.
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Day -21 to Day +100 post-HCT
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Cumulative Incidence of New, Abnormal Cytogenetics
Time Frame: Day 0 to Year 5 post-HCT
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The cumulative incidence of therapy related new, abnormal cytogenetics will be estimated for both groups taking into account the competing risk of death among patients who do not develop a second malignancy.
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Day 0 to Year 5 post-HCT
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Amrita Y. Krishnan MD, MD, City of Hope Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- Immune System Diseases
- Neoplasms
- Lymphoma
- Non-Hodgkin's lymphoma
- Lymphoma, Non-Hodgkin
- Physiological Effects of Drugs
- Antibodies, Monoclonal
- Pharmacologic Actions
- autologous stem cell transplantation
- Lymphoma, B-Cell
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Lymphatic Diseases
- Immunologic Factors
- Neoplasms by Histologic Type
- radioimmunotherapy
- Lymphoma, Large B-Cell, Diffuse
- Zevalin
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antineoplastic Agents, Immunological
- Etoposide
- Rituximab
- Melphalan
- Cytarabine
- Carmustine
Other Study ID Numbers
- 12338
- NCI-2015-00185 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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